This document discusses different types of adrenergic drugs. It describes alpha and beta adrenergic blocking drugs, which are competitive antagonists that inhibit the receptor action of adrenaline. Specific drugs are discussed, including prazosin, terazosin, and doxazosin as selective alpha-1 blockers, and propranolol as a nonselective beta blocker. Their mechanisms of action, pharmacokinetics, uses, interactions and adverse effects are summarized. The document also mentions alpha/beta blockers like labetalol and carvedilol used to treat hypertension and congestive heart failure.

1. ADRENERGIC DRUGS
These are drugs which antagonize the receptor action of adrenaline and related drugs. They are
competitive antagonists at or or both and adrenergic receptors and differ in important ways from
the “adrenergic neurone blocking agents”, which act by interfering with the release of adrenergic
transmitter on nerve stimulation.
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αADRENERGIC BLOCKING DRUGS
These drugs inhibit adrenergic responses mediated through the α adrenergic receptors without
affecting those mediated through receptors.
CLASSIFICATION
A. Nonselective
(i) Ergot alkaloids—Ergotamine, Ergotoxine
(ii) Hydrogenated ergot alkaloids—Dihydroergotamine (DHE),Dihydroergotoxine
(iii) Imidazoline—Phentolamine
(iv) Miscellaneous–Chlorpromazine
B. α 1 selective—Prazosin, Terazosin,Doxazosin, Alfuzosin,Tamsulosin
C. α 2 selective—Yohimbine
Prazosin
This prototype selective α1 antagonist dilates both resistance and capacitance vessels; effect on the former
predominating. The haemodynamic effects, viz reduction in t.p.r. and mean BP accompanied by minor
decrease in venous return and c.o. are similar to that produced by a direct acting vasodilator. However,
unlike hydralazine, there is little reflex cardiac stimulation and renin release during long-term therapy.
Tachycardia does not compensate for the fall in BP, because release inhibitory α 2 (presynaptic) receptors
are not blocked: autoregulation of NA release remains intact. It probably decreases central sympathetic
tone also.
Pharmacokinetics
Prazosin is effective orally (bioavailability ~60%), highly bound to plasma proteins (mainly to 1 acid
glycoprotein), metabolized in liver and excreted primarily in bile. Its plasma t½ is 2– 3 hours; effect of a
single dose lasts for 6–8 hours.
Dose
PRAZOPRES 0.5,1.0 and 2.0 mg tabs. Start with 0.5–1 mg at bedtime; usual dose 1–4 mg BD or TDS.
MINIPRESS XL: Prazosin GITS (gastrointestinal therapeutic system) 2.5 mg and 5 mg tablets; 1 tab OD.
Terazosin
It is chemically and pharmacologically similar to prazosin; differences are higher bioavailability (90%)
and longer plasma t½ (~12 hr); a single daily dose lowers BP over 24 hrs. Terazosin is more popular for
use in BHP due to single daily dose and a probable apoptosis promoting effect on prostate. This is
unrelated to α 1 receptor blockade, but may retard the progression of prostatic hypertrophy.
Dose:HYTRIN,TERALFA,OLYSTER 1, 2, 5 mg tab; usual maintenance dose 2–10 mg OD.
Doxazosin Another long acting (t½ 18 hr) congener of prazosin with pharmacological profile, similar to
terazosin, including the apoptosis promoting effect on prostate. It is used in hypertension and BHP.
Dose: 1 mg OD initially, increase upto 8 mg BD; DOXACARD,DURACARD,DOXAPRESS 1,2, 4 mg
tabs.

2. USES OF αBLOCKERS
1. Pheochromocytoma
2. Hypertension
3. Peripheral vascular diseases
4. Congestive heart failure (CHF)
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ADRENERGIC BLOCKING DRUGS
These drugs inhibit adrenergic responses mediated through the receptors. All blockers are
competitive antagonists. Propranolol blocks 1 and 2 receptors, but has weak activity on 3 subtype. It
is also an inverseagonist: reduces resting heart rate as well. Some blockers like metoprolol, atenolol,
etc. preferentially block 1 receptors, while few others have additional 1 receptor blocking and/or
vasodilator properties.
CLASSIFICATION
Nonselective (1 and 2)
a. Without intrinsic sympathomimetic activity
Propranolol, Sotalol, Timolol.
b. With intrinsic sympathomimetic activity
Pindolol
c. With additionalα blocking property
Labetalol, Carvedilol
Cardioselective (1)
Metoprolol, Atenolol, Acebutolol, Bisoprolol,Esmolol, Betaxolol, Celiprolol, Nebivolol.
PHARMACOLOGICAL ACTIONS OF PROPRANOLOL
1. Propranolol decreases heart rate, force of contraction (at relatively higher doses) and cardiac
output (c.o.).
2. Propranolol blocks vasodilatation and fall in BP evoked by isoprenaline and enhances the rise in
BP caused by Adr.
3. Propranolol increases bronchial resistance by blocking dilator 2 receptors.
4. No overt central effects are produced by propranolol. However,subtle behavioural changes,
forgetfulness, increased dreaming and nightmares have been reported with long-term use of
relatively high doses.
5. Propranolol is as potent a local anaesthetic as lidocaine, but is not clinically used for this purpose
because it causes irritation at the injected site.
6. Relaxation of uterus in response to isoprenaline and selective 2 agonists is blocked by
propranolol.
PHARMACOKINETICS
Propranolol is well absorbed after oral administration, but has low bioavailability due to high first pass
metabolism in liver. Oral: parenteral dose ratio of up to 40:1 has been found. Interindividual variation in
the extent of first pass metabolism is marked—equieffective oral doses vary considerably. Propranolol is
lipophilic and penetrates into brain easily.
A number of metabolites of propranolol have been found, of which the hydroxylated product has
blocking activity. The metabolites are excreted in urine, mostly as glucuronides. More than 90% of
propranolol is bound to plasma proteins.

3. Dose: Oral—10 mg BD to 160 mg QID (average 40–160 mg/ day). Start with a low dose and gradually
increase according to need; i.v.—2 to 5 mg injected over 10 min with constant monitoring. It is not
injected s.c. or i.m. because of irritant property.
INDERAL,CIPLAR 10, 40, 80 mg tab, 1 mg/ml inj.,
BETABLOC 10, 40 mg tab
INTERACTIONS
1. Additive depression of sinus node and A-V conduction with digitalis and verapamil — cardiac
arrest can occur. However, propranolol has been safely used with nifedipine.
2. Propranolol delays recovery from hypoglycaemia due to insulin and oral antidiabetics. Warning
signs of hypoglycaemia mediated through sympathetic stimulation (tachycardia, tremor) are
suppressed. In some cases BP rises due to unopposedα action of released Adr.
3. Phenylephrine, ephedrine and other αagonists present in cold remedies can cause marked rise in
BP due to blockade of sympathetic vasodilatation.
4. Indomethacin and other NSAIDs attenuate the antihypertensive action of blockers.
5. Cimetidine inhibits propranolol metabolism. However, the dose range of propranolol is wide, and
this may not be clinically significant.
6. Propranolol increases bioavailability of chlorpromazine by decreasing its first pass metabolism.
ADVERSE EFFECTS AND CONTRAINDICATIONS
1. Propranolol can accentuate myocardial insufficiency and can precipitate CHF/edema
2. Propranolol worsens chronic obstructive lung disease, can precipitate life-threatening attack of
bronchial asthma: contraindicated in asthmatics
3. Plasma lipid profile is altered on long term use.
4. Withdrawal of propranolol after chronic use should be gradual, otherwise rebound hypertension,
worsening of angina and even sudden death can occur.
5. Propranolol is contraindicated in partial and complete heart block: arrest may occur.
6. Cold hands and feet,worsening of peripheral vascular disease are noticed due to blockade of
vasodilator 2 receptors.
USES
1. Hypertension
2. Angina pectoris
3. Cardiac arrhythmias
4. Myocardial infarction
5. Congestive heart failure
6. Glaucoma
α + ADRENERGIC BLOCKERS
Labetalol
It is a combined αand blocker; reduces t.p.r. and acts faster than pure blockers. It has been used i.v.
for rapid BP reduction in hyperadrenergic states, cheese reaction, clonidine withdrawal, eclampsia, etc.
Oral labetalol therapy is restricted to moderately severe hypertension not responding to a pure blocker,
because side effects of both αblocker and blocker occur with it.
Carvedilol
This nonselective + weak selective α1 blocker produces vasodilatation and has additional
antioxidant/free radical scavenging properties. Whether these ancilliary properties confer any superiority
is not known. Carvedilol is a frequently selected drug for long-term treatment of CHF, and is approved as
an antihypertensive as well. Side effects are similar to labetalol; liver enzymes may rise in some.